Chapter Two: Fact Sheet: PB Pretreatment for Soman Exposure
The following synopsis serves as a brief review of PB, its function and
What is PB?
- Pyridostigmine bromide is a chemical that blocks the
nerve-signal-regulating enzyme acetylcholinesterase (AChE). It is given
as a pill to military personnel during periods of high threat of chemical
warfare attack to prevent death in the event of exposure to the nerve agent
- It is used as an adjunct to postexposure administration of atropine and
pralidoxime and confers no protection in the absence of these treatments.
How Nerve Agents Work
- Soman, like other nerve agents, acts by inhibiting AChE, the enzyme that
breaks down the body's acetylcholine (ACh), a neurotransmitter crucial to
regulation of voluntary and involuntary muscles and to function of the brain.
- Once AChE is inhibited, ACh accumulates and may cause death from respiratory
- In addition to spasms of the airways and reduced breathing drive, other
effects of soman include slowed heart rate; increased secretions from the nose,
eyes, intestines, salivary glands, sweat glands, and airways; increased
movement of the intestines; twitching, weakness, and paralysis; loss of
consciousness; and seizures.
How Traditional Anti-Nerve Agents Work
Atropine and Pralidoxime
What Is Aging?
- Atropine is the mainstay of postexposure antidote treatment for nerve
agent exposure. Atropine opposes the effects of acetylcholine. (It opposes
the "muscarinic effects"--see Chapter 3.) Rapid administration of atropine (by
injection) is essential for severe nerve agent casualties.
- Pralidoxime (or other oximes), administered by injection, assists in
postexposure treatment. Oximes have the ability to cause nerve agents to be
removed from AChE. However, they are ineffective once a process called "aging"
How PB Works
- Aging is a chemical change that happens to the AChE-nerve agent
complex. Aging results in permanent inactivation of the AChE. Aging happens
quickly in the case of the soman-AChE complex--half of complexed agents will
have aged within a couple of minutes--whereas it takes hours for comparable
aging to occur for other nerve agents, such as sarin.
- Once aging has occurred, oxime therapy is ineffective.
PB Is Used When Soman Is a Danger
- PB is a carbamate compound that is thought to protect AChE by reversibly
binding to ("carbamylating") it, so that the nerve agent cannot bind to it. It
may also assist in protection against nerve agent by "desensitizing" ACh
- PB is preferred over other carbamylators because it usually does not
penetrate the central nervous system. Consequently, PB minimizes any harmful
effects on brain function and does not significantly disable mental performance
in those who take it.
- PB is needed for adequate protection against soman: It takes only two
minutes for 50 percent of the AChE-soman complexes to "age," permanently
inactivating AChE. Since this reaction time is so short, personnel do not have
enough time after they have been exposed to soman to realize they have been
exposed to a nerve agent, to take oxime, and to allow oxime to pull nerve agent
off AChE. Before all that can be done, most of the soman will have undergone
aging, permanently inactivating the bound AChE. However, if personnel take PB
in advance of exposure, soman will be prevented from binding to AChE in
PB-bound AChE molecules, and aging cannot take place with permanent
inactivation of these AChE molecules. The armed forces estimate that during a
chemical attack, many personnel may be exposed to five times the lethal dose of
nerve agent, so a "protective ratio" (the factor by which a treatment raises
the lethal dose) of at least five is needed. Addition of PB allows the
protective ratio to exceed five for soman, based on studies in monkeys.
- PB is not needed against sarin: It takes five hours for 50 percent of
the AChE-sarin complexes to age. PB pretreatment does not confer an advantage
against sarin, based on studies in animals; personnel have enough time to take
oxime after exposure to this nerve agent before aging takes place, reactivating
the AChE molecule. Indeed, soman is the only nerve agent for which PB is known
to be necessary to produce an adequate protective ratio.